Overview

Many pediatric cancers initially respond to treatment, but tumors subsequently return after treatment is finished. Our lab is identifying the mechanisms driving tumor cell recurrence. Additionally, we study the tumor microenvironment to better understand why some types of tumor cells are more responsive to chemotherapy and immunotherapy compared to others. We use a combination of single-cell sequencing and patient-derived models of cancer to study and model tumor biology. Our discoveries identify new avenues for the treatment of pediatric cancers, with the goal of delivering long-term responses for our patients.

photo of jars in lab

Patel research summary

Tumor recurrence is a major barrier to achieving durable cures in patients with cancer. Yet, there are major gaps in our understanding of the biological mechanisms underlying disease persistence and recurrence. Pediatric cancers present a unique opportunity to study the intersection of normal development, oncogenesis and therapy resistance.

Pediatric rhabdomyosarcoma is a soft tissue sarcoma with a notoriously high rate of recurrence after treatment ceases. Up to 70% of patients with metastatic disease experience disease recurrence. Children who have recurrent disease have poor outcomes, underscoring the importance of understanding tumor cell persistence during therapy and finding novel treatment options to prevent recurrence. 

hands working in lab

Our lab investigates the mechanisms of treatment persistence and recurrence in pediatric cancers such as rhabdomyosarcoma. We use patient samples and experimental patient-derived models to investigate tumor evolution during therapy. Using single-cell sequencing and spatial technologies, we developed methods to track and identify the rare malignant cells that persist during therapy. Additionally, we have an interest in understanding how the non-malignant cells of the tumor microenvironment–fibroblasts, immune cells and endothelium– contribute to persistence. Ultimately, our goal is to leverage the molecular mechanisms of tumor persistence to identify exploitable vulnerabilities and develop novel treatment options.

We use a combination of well-established and emerging techniques, including single cell sequencing, spatial transcriptomics, computational biology, patient-derived xenografts, spheroids and 3D-printed tumor models to address our scientific questions. 

Mechanisms of recurrence

Rhabdomyosarcoma can be molecularly classified into two major molecular subtypes: fusion-negative or fusion-positive rhabdomyosarcoma. In fusion-negative rhabdomyosarcoma, we have identified rare cells that mimic early muscle progenitors that survive treatment and rapidly regenerate to propagate tumors. In contrast, we found that fusion-positive rhabdomyosarcoma cells do not have progenitor-like cells, and malignant cells undergo a transition into non-myogenic lineages during therapy. However, the molecular mechanism underlying how each cell population contributes to recurrence remains unclear. We aim to better our understanding of what defines and regulates these tumors cells, thereby enabling them to regenerate tumors after therapy. 

Understanding the tumor microenvironment

The incorporation of antibodies targeted against the disialoganglioside GD2 (anti-GD2) has dramatically improved outcomes for children diagnosed with high-risk neuroblastoma. These clinical responses demonstrate that the immune system, when harnessed correctly, can be deployed to treat pediatric cancers. By studying the tumor microenvironment, we gain valuable insight into the molecular interplay between immune and malignant cells in treated and untreated tumors. Using this information, we aim to identify biomarkers for response in neuroblastoma and to find analogous immunotherapy targets in other pediatric solid tumors.

Publications

About Anand G. Patel

Dr. Patel is a pediatric oncologist who received his MD and PhD from the Mayo Clinic in Rochester, Minnesota. He completed internship and residency in general pediatrics at St. Louis Children’s Hospital/Washington University in St. Louis, and clinical fellowship in Pediatric Hematology/Oncology at St. Jude Children’s Research Hospital. In 2020 he was selected as a Damon Runyon Sohn-Pediatric Cancer Research fellow. He has been honored as an AACR NextGen Star and was awarded the 2022 Damon Runyon Jake Wetchler Award for Pediatric Innovation. Dr. Patel is interested in understanding the mechanisms driving recurrence in pediatric cancers, understanding the interplay between malignant cells and the tumor microenvironment and building computation tools to decipher shared molecular features of pediatric solid tumors. 

Contact us

Anand G. Patel, MD, PhD
Assistant Member

Department of Oncology
Solid Tumor Division
MS 322, Room M2363

St. Jude Children's Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
(901) 595-7768 anand.patel2@stjude.org

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262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
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